Somatic cell hybridization studies have clearly demonstrated the phenomenon of suppression of tumorigenicity. We intend to identify the gene(s) involved in tumor suppression and characterize their function. Initially, single chromosome (microcell) transfers will be used to identify specific chromosome(s) that carry the tumor-suppressor gene(s). Subtractive cDNA hybridization procedures will be used to clone these genes. We shall also investigate the interaction between tumor- suppressor gene(s) and oncogenes. The relevant genes will be inserted into expression vectors, containing an inducible MMTV- LTR promoter, in both sense and anti-sense orientations. The effect of varying the level of sense and anti-sense expression of these genes will be examined. We have already identified a candidate recessive oncogene product (p75 tumor antigen). We intend to clone and characterize the gene encoding p75 and investigate its role in tumorigenic behavior of HeLa cells. The trans-acting gene that regulates expression of p75 will also be cloned and characterized. The possibility that this trans-acting regulatory gene is a tumor- suppressor gene will be examined.